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MGD014 in HIV-Infected Individuals on Suppressive Antiretroviral Therapy

Primary Purpose

HIV-1-infection

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

MGD014

About this trial

This is an interventional treatment trial for HIV-1-infection focused on measuring HIV, Latent HIV-1 infection, HIV therapy, antibody-based therapy

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Ability and willingness of participant to provide written informed consent.
HIV-1 infection, documented by any FDA-approved rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load.
On a potent, stable, continuous ART regimen for ≥ 24 months prior to Screening.
Plasma HIV-1 RNA < 50 copies/mL at two time points in the previous 12 months prior to screening (one time point can be screening) and never ≥ 50 copies/mL on 2 consecutive time points in the last 24 months.
Adequate organ function based on acceptable laboratory parameters.

Exclusion Criteria:

Women of childbearing potential defined as any female who has experienced menarche and who has not undergone successful surgical sterilization or menopause.
History or other evidence of severe illness, immunodeficiency other than HIV, or any other condition that would make the potential participant unsuitable for study.
History or other evidence of any condition or process for which signs or symptoms could be confused with reactions to MGD014.
History of any HIV immunotherapy or HIV vaccine except for MGD014 within 12 months prior to screening.
History of clinically significant cardiovascular disease, severe allergic reactions, malignancy (except non-melanoma skin cancer) within 5 years, seizure disorder within 2 years, organ/tissue transplant, autoimmune disease, unstable asthma, bleeding disorder.
Evidence of active viral, or antifungal treatment within 7 days prior to the initiation of study drug
Active, asymptomatic, or suspected COVID-19/SARS-CoV-2 infection.
Active, untreated syphilis.
Use of blood products, cytokine therapy, growth-stimulating factors, cytotoxic chemotherapy or investigational therapy within 90 days.
Current use of the antivirals maraviroc and/or enfuvirtide.
Any vaccination with exception of flu vaccine within 30 days of screening.

Sites / Locations

University of North Carolina Chapel Hill

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm Type

Experimental

Arm Label

MGD014 0.1 micrograms/kilogram (mcg/kg)

MGD014 0.3 mcg/kg

MGD014 1.0 mcg/kg

MGD014 3.0 mcg/kg

MGD014 10.0 mcg/kg

MGD014 30.0 mcg/kg

MGD014 100.0 mcg/kg

MGD014 300.0 mcg/kg

MGD014 300.0 mcg/kg multiple doses

Arm Description

a single 2-hour infusion

2-hour infusion every 2 weeks for 3 infusions

Outcomes

Primary Outcome Measures

Number of Participants With Treatment-Emerging Adverse Events

Safety is based on evaluation of adverse events (AEs) and serious adverse events (SAEs) from the time of study drug administration through the End of Study visit.

Secondary Outcome Measures

AUC Inf: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity of MGD014

AUCinf, area under the concentration-time curve from the time of dose extrapolated to time infinity and reflects total drug exposure

Cmax: Maximum Plasma Concentration

Cmax is the maximum (or peak) serum concentration of a drug in the body after the drug has been administered

Tmax: Time to Maximum Concentration

Tmax is the time it takes a drug to reach the maximum concentration

Ctrough: Trough Level Concentration

a trough level or trough concentration (Ctrough) is the concentration reached by a drug immediately before the next dose is administered,

Clearance

Total body clearance of the drug from plasma of MGD014

Vz: Terminal Phase Volume of Distribution of MGD014

The ratio of the total quantity of drug in the body to drug plasma concentration during the elimination

Terminal Half Life of MGD014

The half-life is the amount of time required for 50% of the drug to be removed from the body

Number of Participants That Developed Antidrug Antibodies to MGD014

Number of participants with antidrug antibodies to MGD014

Number of Participants With Increased Cytokine Levels

Number of participants with increased cytokine levels from baseline after MGD014 administration. This safety measure compares serum cytokine levels obtained prior to dosing with levels obtained after dosing. Increased cytokines can be a measure of T-cell activation in response to MGD014 binding. Cytokines analyzed included interferon-gamma, tumor necrosis factor-alpha, interleukin (IL)2, IL-5, IL-6, and IL-10.

Full Information

NCT ID

NCT03570918

First Posted

June 18, 2018

Last Updated

August 31, 2022

Sponsor

MacroGenics

Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

1. Study Identification

Unique Protocol Identification Number

NCT03570918

Brief Title

MGD014 in HIV-Infected Individuals on Suppressive Antiretroviral Therapy

Official Title

A Phase 1 Study to Evaluate the Safety, Immunologic and Virologic Responses of MGD014 Therapy in HIV-Infected Individuals on Suppressive Antiretroviral Therapy

Study Type

Interventional

2. Study Status

Record Verification Date

August 2022

Overall Recruitment Status

Completed

Study Start Date

September 25, 2018 (Actual)

Primary Completion Date

September 28, 2021 (Actual)

Study Completion Date

September 28, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

MacroGenics

Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This is a Phase 1, open-label single-center study to determine the safety of MGD014 in participants with human immunodeficiency virus (HIV) infection on stable suppressive antiretroviral therapy (ART).

Detailed Description

Eligible participants will be maintained on ART and receive either one infusion (Part 1) or multiple infusions of MGD014 (Part 2). Part 1 is a single ascending dose study with a 1+3 design for the first 2 dose cohorts, and a 3+3 design with staggered accrual for the 6 higher dose cohorts, with an aim of determining the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of ascending doses up to either the Optimal Biologic Dose (OBD) or the maximum administered dose (MAD). Part 2 is a multi-dose expansion cohort with MGD014 administered at the OBD, as determined in Part 1. In Part 2, additional assessments on the effects of MGD014 on HIV latent infection parameters will be evaluated.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV-1-infection

Keywords

HIV, Latent HIV-1 infection, HIV therapy, antibody-based therapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Model Description

Open-label dose-escalation study

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

21 (Actual)

8. Arms, Groups, and Interventions

Arm Title

MGD014 0.1 micrograms/kilogram (mcg/kg)

Arm Type

Experimental

Arm Description

a single 2-hour infusion

Arm Title

MGD014 0.3 mcg/kg

Arm Type

Experimental

Arm Description

a single 2-hour infusion

Arm Title

MGD014 1.0 mcg/kg

Arm Type

Experimental

Arm Description

a single 2-hour infusion

Arm Title

MGD014 3.0 mcg/kg

Arm Type

Experimental

Arm Description

a single 2-hour infusion

Arm Title

MGD014 10.0 mcg/kg

Arm Type

Experimental

Arm Description

a single 2-hour infusion

Arm Title

MGD014 30.0 mcg/kg

Arm Type

Experimental

Arm Description

a single 2-hour infusion

Arm Title

MGD014 100.0 mcg/kg

Arm Type

Experimental

Arm Description

a single 2-hour infusion

Arm Title

MGD014 300.0 mcg/kg

Arm Type

Experimental

Arm Description

a single 2-hour infusion

Arm Title

MGD014 300.0 mcg/kg multiple doses

Arm Type

Experimental

Arm Description

2-hour infusion every 2 weeks for 3 infusions

Intervention Type

Biological

Intervention Name(s)

MGD014

Intervention Description

HIV-1 x CD3 bispecific DART molecule

Primary Outcome Measure Information:

Title

Number of Participants With Treatment-Emerging Adverse Events

Description

Safety is based on evaluation of adverse events (AEs) and serious adverse events (SAEs) from the time of study drug administration through the End of Study visit.

Time Frame

up to 77 days

Secondary Outcome Measure Information:

Title

AUC Inf: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity of MGD014

Description

AUCinf, area under the concentration-time curve from the time of dose extrapolated to time infinity and reflects total drug exposure

Time Frame

Study Day 0 to 42

Title

Cmax: Maximum Plasma Concentration

Description

Cmax is the maximum (or peak) serum concentration of a drug in the body after the drug has been administered

Time Frame

Study Day 0

Title

Tmax: Time to Maximum Concentration

Description

Tmax is the time it takes a drug to reach the maximum concentration

Time Frame

Study Day 0

Title

Ctrough: Trough Level Concentration

Description

a trough level or trough concentration (Ctrough) is the concentration reached by a drug immediately before the next dose is administered,

Time Frame

Study Day 14

Title

Clearance

Description

Total body clearance of the drug from plasma of MGD014

Time Frame

Study Day 0 to 42

Title

Vz: Terminal Phase Volume of Distribution of MGD014

Description

The ratio of the total quantity of drug in the body to drug plasma concentration during the elimination

Time Frame

Study Day 1, 2, 7, 14, 21, 28, and 42 (single infusion) and Study Day 1, 3, 14, 28, 42, and 77 (multiple infusions)

Title

Terminal Half Life of MGD014

Description

The half-life is the amount of time required for 50% of the drug to be removed from the body

Time Frame

Study Day 0 to Study Day 42

Title

Number of Participants That Developed Antidrug Antibodies to MGD014

Description

Number of participants with antidrug antibodies to MGD014

Time Frame

Study Day 1, 14, 28 and 42 (single infusion) and Study Day 1, 14, 28 and 77 (multiple infusions)

Title

Number of Participants With Increased Cytokine Levels

Description

Time Frame

Study Day 1, 2 and 7 (single infusion) and Study Day 1, 3, 14 and 28 (multiple infusions)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Ability and willingness of participant to provide written informed consent. HIV-1 infection, documented by any FDA-approved rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load. On a potent, stable, continuous ART regimen for ≥ 24 months prior to Screening. Plasma HIV-1 RNA < 50 copies/mL at two time points in the previous 12 months prior to screening (one time point can be screening) and never ≥ 50 copies/mL on 2 consecutive time points in the last 24 months. Adequate organ function based on acceptable laboratory parameters. Exclusion Criteria: Women of childbearing potential defined as any female who has experienced menarche and who has not undergone successful surgical sterilization or menopause. History or other evidence of severe illness, immunodeficiency other than HIV, or any other condition that would make the potential participant unsuitable for study. History or other evidence of any condition or process for which signs or symptoms could be confused with reactions to MGD014. History of any HIV immunotherapy or HIV vaccine except for MGD014 within 12 months prior to screening. History of clinically significant cardiovascular disease, severe allergic reactions, malignancy (except non-melanoma skin cancer) within 5 years, seizure disorder within 2 years, organ/tissue transplant, autoimmune disease, unstable asthma, bleeding disorder. Evidence of active viral, or antifungal treatment within 7 days prior to the initiation of study drug Active, asymptomatic, or suspected COVID-19/SARS-CoV-2 infection. Active, untreated syphilis. Use of blood products, cytokine therapy, growth-stimulating factors, cytotoxic chemotherapy or investigational therapy within 90 days. Current use of the antivirals maraviroc and/or enfuvirtide. Any vaccination with exception of flu vaccine within 30 days of screening.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Chief Medical Officer

Organizational Affiliation

MacroGenics

Official's Role

Study Director

Facility Information:

Facility Name

University of North Carolina Chapel Hill

City

Chapel Hill

State/Province

North Carolina

ZIP/Postal Code

27599

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

MGD014 in HIV-Infected Individuals on Suppressive Antiretroviral Therapy

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